tbuckley/cabot-search huggingface dataset:
Self-reported overall wellbeing and physical function among chemotherapy and surgery patients completing symptom questionnaires across six health systems.
Authors: Michael J. Hassett, Christine Cronin, Angela Tramontano, Sandra L. Wong, Hajime Uno, Roshan Paudel, Jessica J Bian, Don S. Dizon, Hannah W. Hazard-Jenkins, Raymond U. Osarogiagbon, Deborah Schrag
Journal: Journal of Clinical Oncology (2023)

12110 Background: Health systems have begun using electronic patient reported outcomes (ePROs) to evaluate and ideally mitigate patients’ symptom burden following treatment for cancer and other conditions. However, the optimal number of symptoms and approach to capturing this information is unknown. We hypothesized that self-reported overall wellbeing (OWB) and physical function (PFN) would provide distinctive information, beyond that described by a multi-item symptom questionnaire, and augment the clinical utility of an ePRO system. Methods: eSyM, an EHR-integrated symptom management program, was deployed across six health systems for patients receiving chemotherapy or surgery for a suspected or confirmed thoracic, gastrointestinal, or gynecologic malignancy. eSyM prompts patients to complete a 12-item symptom questionnaire 2-3 times per week. This questionnaire also includes two pictogram questions that assess OWB and PFN – each scored using a four-point scale from 0 (best) to 3 (worst). We sought to identify patient characteristics associated with the lowest OWB and PFN (i.e., score = 3), to describe Spearman correlations between OWB and PFN, and to elucidate the relationships between symptom scores and OWB/PFN. Ordinal logistic regression models were used to adjust for potential confounding. Results: From September 2019-December 2022, 9753 patients submitted 75,166 questionnaires. There were 3846 chemotherapy patients (median age 66, 58% female, 17% non-white) and 5907 surgery patients (median age 61, 73% female, 7% non-white). The plurality of responses indicated mild impairment for OWB and PFN (Table). OWB and PFN scores were moderately correlated with each other (chemotherapy 0.62; surgery 0.59); with the sum of all symptom scores for chemotherapy (OWB 0.48, PFN 0.45) and surgery (OWB 0.51, PFN 0.45) patients; and with pain, fatigue, and anorexia (correlation coefficients 0.40-0.61). No individual symptoms were strongly correlated (coefficient &gt; 0.7) with OWB or PFN. After controlling for other factors, OWB and PFN scores varied significantly by health system. Patients with disability were more likely to report low OWB and PFN (ORs 1.99-3.26; p &lt; 0.05) versus other employment statuses. Conclusions: In a large cohort of chemotherapy and surgery patients from six community-based cancer centers, self-reported OWB and PFN scores were moderately correlated with common symptoms. These items offer discriminant and face validity and provide distinctive information that supplements a multi-item symptom questionnaire. Routine use of OWB and PFN can guide management strategies for symptomatic cancer patients. Clinical trial information: NCT03850912 . [Table: see text]
Respiratory toxicities after concurrent chemoradiotherapy and subsequent consolidation immune checkpoint inhibitors in locally advanced non-small cell lung cancer: Infectious and non-infectious subtypes by pathogen NGS testing.
Authors: Bo Qiu, Mai Xiong, FangJie Liu, PengXin Zhang, Rui Zhou, DaQuan Wang, YiFeng Luo, YiMei Liu, JinYu Guo, NaiBin Chen, Shiyue Li, Hui Liu
Journal: Journal of Clinical Oncology (2023)

e20557 Background: Consolidation immune checkpoint inhibitors (ICIs) following concurrent chemoradiotherapy (CCRT) have significantly improved survival in locally advanced non-small cell lung cancer (LA-NSCLC), while the associated respiratory toxicities were of particular concern. We aimed to investigate the &gt; = G2 respiratory toxicities, the characteristics of concomitant infection, and provide detailed information for clinical management. Methods: We reviewed 77 LA-NSCLC patients treated with CCRT and consolidation ICIs. The details of &gt; = G2 respiratory toxicities and concomitant infection were analyzed. Potential risk factors for &gt; = G2 respiratory toxicities were explored by univariable and multivariable analysis. Respiratory toxicities were collected from the start of consolidation ICIs till 6 months after the last infusion of ICIs. Concomitant infection was defined as positive findings from next-generation sequencing (NGS) of bronchoalveolar lavage sampling. Results: Patients were treated with definitive radiotherapy at a median dose of 60 Gy (IQR, 60-64), concurrently with weekly docetaxel and platinum and followed by single-agent ICIs. The median duration of consolidation ICIs was 5.4 months (IQR, 2.3-8.2). Twenty-six patients (33.8%) experienced &gt; = G2 respiratory toxicities by a median of 4.8 months (IQR 1.5-6.6) after initiation of consolidation ICIs. Pneumonitis (14, 18.2%) and tracheobronchitis (13, 16.9%) were the most common &gt; = G2 respiratory disorders. Location of primary tumor (p = 0.027) and the proportion of CD3+ lymphocyte before consolidation ICIs (p = 0.044) were independent risk factors for the occurrence of &gt; = G2 respiratory toxicities. Eleven patients (14.3%) had &gt; = G2 respiratory toxicities and concomitant infection. Identified pathogens included bacteria (n = 9), Aspergillus (n = 5), Pneumocystis (n = 1) and Leptosvirus (n = 1). Concomitant infection was more commonly detected in patients with tracheobronchitis compared with those with pneumonitis ( p= 0.002), was associated with a higher grade of toxicity ( p= 0.050) and relatively poorer outcome after management ( p= 0.002). Conclusions: Respiratory toxicities after CCRT and subsequent consolidation ICIs in LA-NSCLC mainly included pneumonitis and tracheobronchitis, and could be separated into infectious and non-infectious subtypes. Bacteria and Aspergillus were the predominant pathogens. Our findings highlight the importance of the bronchoscopy and pathogen NGS testing to detect airway disease and specific infection. Long-term systemic steroids might adversely affect respiratory toxicities with concomitant opportunistic infection, which should be taken into account at the onset of management.
Response-adapted therapy (tx) with nivolumab plus brentuximab vedotin (nivo + BV) without autologous hematopoietic cell transplantation (auto-HCT) in children, adolescents, and young adults (CAYA) with low-risk relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL): CheckMate 744.
Authors: Paul David Harker-Murray, Peter D. Cole, Bradford S. Hoppe, David C. Hodgson, Auke Beishuizen, Nathalie Garnier, Salvatore Buffardi, Maurizio Mascarin, Andrej Lissat, Alev Akyol, Russell Crowe, Ju Li, Richard A. Drachtman, Kara M Kelly, Thierry Leblanc, Stephen Daw
Journal: Journal of Clinical Oncology (2023)

7515 Background: Outcomes are poor for patients (pts) with cHL who develop R/R disease after first-line (1L) chemotherapy ± radiotherapy (RT). Salvage tx that attain high event-free survival (EFS) rates and minimize late toxicity by omitting high-dose chemotherapy (HDCT)/auto-HCT are needed. CheckMate 744 (NCT02927769) is the first multicenter phase 2 study evaluating a risk-stratified, response-adapted salvage tx with nivo + BV in CAYA with R/R cHL. In the standard-risk cohort, complete molecular response (CMR) rate before consolidation with HDCT/auto-HCT was 94% (Harker-Murray et al. Blood 2022). With highly active salvage tx, pts in low-risk cohort could achieve high EFS without HDCT/auto-HCT; we report data from this cohort. Methods: Pts were aged 5–30 y and had ≤ 3 cycles (C) of 1L anthracycline-based systemic tx. Risk stratification was described in Harker-Murray et al. Pts received 4C of nivo + BV induction. Pts with CMR received additional 2C nivo + BV before involved-site radiation therapy (ISRT) consolidation (dose, 30–30.6 Gy). Pts with suboptimal response received 2C BV + bendamustine intensification; pts with CMR proceeded to ISRT consolidation. Primary endpoints: CMR rate (Lugano 2014) any time before ISRT and 3-y EFS rate, both per blinded independent central review (BICR). For CMR and overall response rate (ORR), a 90% confidence interval (CI) was used per statistical plan. Results: Among 28 pts treated with nivo + BV, median (range) age was 17 (6–27) y; 64% of pts were aged &lt; 18 y. Most (64%) pts had stage II disease at relapse; 82% had relapse ≥ 12 mo after 1L tx, 2 pts had prior RT. Median (range) follow-up was 31.9 (2.2–55.3) mo. CMR, ORR, 3-y EFS and PFS rates are shown in Table. Median duration of response was not reached; 87% of pts had sustained response at 36 mo’ follow-up. Efficacy outcomes were comparable in the pediatric population (CMR per BICR before ISRT, 88.9%; 3-y EFS rate, 78.3%). During induction, 22 (78.6%) pts had treatment-related adverse events (TRAEs; grade 3/4, 25.0% pts; hematologic, &lt; 10% pts; immune-mediated, 21.4%). Serious AEs leading to discontinuation included rash, pyrexia, and acute kidney injury (1 pt each). Conclusions: The findings demonstrate that most CAYA with low-risk R/R cHL can be salvaged with chemoimmunotherapy with a favorable toxicity profile, and do not require HDCT/auto-HCT. Clinical trial information: NCT02927769 . [Table: see text]
Medicaid enrollment changes among U.S. adult survivors of childhood cancer following medicaid expansion: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Xu Ji, Xin Hu, Ann C. Mertens, Wendy M. Leisenring, Paul C. Nathan, Gregory T. Armstrong, Sharon M. Castellino, Anne C. Kirchhoff
Journal: Journal of Clinical Oncology (2023)

10011 Background: Little is known about whether Medicaid expansion under the Affordable Care Act (ACA) affected insurance coverage among adult survivors of childhood cancer, a population at high-risk for poor health outcome. We addressed this gap by evaluating the association between ACA Medicaid expansion and Medicaid enrollment among participants in the Childhood Cancer Survivor Study (CCSS). Methods: The CCSS cohort of 5-year survivors of childhood cancer was linked to administrative Medicaid insurance data in 2010-2016. We identified 13,895 adult survivors (aged 18-64 years) diagnosed with cancer under age 21 and between 1970 and 1999. Outcomes included (1) percentage with any Medicaid enrollment by year; and (2) Medicaid-covered days (number of days when a survivor was enrolled in Medicaid) during each year. Multivariable difference-in-differences (DD) models were used to examine outcome changes pre vs. post ACA Medicaid expansion, in expansion- vs. non-expansion states, adjusting for age, sex, race/ethnicity, income, education, and chronic conditions. Multivariable models were conducted overall and then stratified by cancer type, race/ethnicity, income, and education. Results: Medicaid enrollment rates increased more in expansion states (17.6% pre-expansion to 24.1% post-expansion) than non-expansion states (16.4% to 16.9%), leading to a net increase in enrollment of 6.6 percentage points (ppt; 95% CI = 5.5-7.7) in the multivariable DD model. Multivariable DD model showed a net increase of 18.4 days (95% CI = 13.8-23.1) in Medicaid-covered days in expansion states relative to non-expansion states. The expansion-associated increase in Medicaid enrollment rates was greatest among survivors of leukemia (multivariable DD estimate: 8.9 ppt, 95% CI = 6.9-11.0) and non-Hodgkin lymphoma (8.0 ppt, 95% CI = 5.0-10.9). Greater increases in Medicaid enrollment were seen in non-Hispanic Black (13.5 ppt, 95% CI = 8.0-19.1) and Hispanic survivors (15.8 ppt, 95% CI = 10.6-21.0) than non-Hispanic White peers (5.1 ppt; 95% CI = 4.0-6.2); in survivors with &lt; $20K household income (11.7 ppt, 95% CI = 8.9-14.4) compared to those with ≥$60K household income (2.9 ppt, 95% CI = 1.6-4.2); and in survivors with high school or lower education (9.3 ppt, 95% CI = 6.9-11.8) compared to those with a college or higher degree (3.9 ppt, 95% CI = 2.6-5.3). Similar patterns were observed across survivor subgroups when examining Medicaid-covered days. Conclusions: We provide the first evidence on increased Medicaid enrollment and longer coverage duration among adult survivors of childhood cancer following Medicaid expansion, with greater increases seen among survivors of underrepresented racial/ethnic populations, those with low socioeconomic status, and high medical need survivors.
Role of HLA-DRB4 as a biomarker for endocrine toxicity and survival outcomes after immunotherapy in metastatic non-small cell lung cancer.
Authors: Cindy Jiang, Shashidhar Ravishankar, Lili Zhao, Michael Green, Andrea Towlerton, Anthony Scott, Malini Raghavan, Matthew Cusick, Edus H. Warren, Nithya Ramnath
Journal: Journal of Clinical Oncology (2023)

e21005 Background: Immune checkpoint inhibitors (ICI) have significantly improved outcomes in non-small cell lung cancer (NSCLC) but are associated with development of immune related adverse events (irAEs). Currently, the role of germline determinants on immunotherapy efficacy and toxicity is unclear. Human leukocyte antigen (HLA) is emerging as a possible predictive biomarker. Our study aimed to assess HLA class II genotypes and their correlation to irAEs and survival. Methods: We conducted a single institution, prospective study with collection of baseline blood samples in patients with metastatic NSCLC treated with ICIs. Clinical characteristics and HLA genotypes (ScisGo HLA typing kits) were obtained. Kaplan-Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Cox regression model was used for multivariate analysis (MVA) and we adjusted for age, gender, race, stage, and histology. Cumulative incidence function was used for association between HLA-DRB4 and endocrine irAEs. Results: Among 98 eligible patients, 85 had complete HLA genotyping. Most patients were men (96.5%), Caucasian (75.3%), and former/active smokers (98.8%) with a median age of 72 years. Median follow up time was 42.8 months. Majority of patients received pembrolizumab (83.5%). Other ICIs included durvalumab (10.6%) and nivolumab (4.7%). Twenty patients (23.5%) experienced irAEs – 11 patients had endocrine irAEs and 9 with other irAEs. 3 patients (27.3%) with endocrine irAEs had toxicity grade 3. Presence of irAE did not improve PFS (p = 0.226, HR 0.61, 95% CI [0.268,1.365]) or OS (p = 0.219, HR 0.63, 95% CI [0.301,1.316]). HLA-DRB4 was present in 39/85 patients (45.9%) and was the predominant genotype in patients with endocrine irAE (9/11, 81.8%) (Table 1). The cumulative incidence of endocrine irAEs was higher in patients expressing HLA-DRB4 (p = 0.0139 ). HLA-DRB4 improved survival in both univariate (PFS 9.9 months, p = 0.040; OS 26.3 months, p = 0.0085) and MVA (PFS p = 0.0310, HR 0.55, 95% CI [0.31, 0.95]); OS p = 0.003, HR 0.40, 95% CI [0.21, 0.73]). Conclusions: Expression of HLA-DRB4 was associated with the development of endocrine irAEs and correlated with improved survival outcomes in metastatic NSCLC patients being treated with ICIs. Further studies are necessary to validate our findings of HLA-DRB4 as a possible predictive marker for endocrine irAEs and therapy efficacy.[Table: see text]
Using key stakeholder interviews to inform implementation of a cancer center collaborative intervention to improve clinical trial accruals.
Authors: Pakhi Goel, Sylvia Lin, Nina A. Bickell, Cardinale B. Smith, Grace C. Hillyer, Karyn A. Goodman, Megan C. Edmonds
Journal: Journal of Clinical Oncology (2023)

e18650 Background: Cancer clinical trial (CT) participation rates in the US are low, especially among BIPOC populations. Patient enrollment to CTs is influenced by structural characteristics of the care delivery system, and the nature of individual needs and available resources. We are developing a multi-level intervention across 3 cancer centers in New York City by creating a collaborative pool of, and a referral system for breast, prostate, and liver cancer CTs to increase overall participation, particularly among BIPOC populations. To inform implementation of this intervention, we explored key stakeholder perceptions and attitudes around CT enrollment process across 3 hospitals within one such cancer center. Methods: We conducted semi-structured interviews with 23 key stakeholders to determine the attitudinal and structural factors affecting CT accrual at 1 cancer center and its 2 community hospital affiliates. Stakeholders included oncologists, nurses, informaticists, oncology leadership and research staff, identified using a targeted and snowball sampling approach. Guided by the Behavioral Model of Health Service Use, we identified themes related to enabling, predisposing, and need factors, and coded transcripts until theme saturation in Dedoose. Results: Key approaches to improve CT participation focused on these structural enabling themes: increased availability of CTs, personnel to screen and enroll patients, well-timed and technology-assisted clinician notification of a potential CT match (within or outside home institution), along with an institutional culture encouraging stakeholder engagement, provider outreach, and care coordination. Important predisposing and enabling themes related to stakeholders’ beliefs about patients included: financial access, knowledge and perceptions about CTs, language barriers, motivation, and medical mistrust. Knowledge about open trials, and skepticism or enthusiasm about CTs were important predisposing themes related to clinicians. Need theme affecting implementation was clinician judgment about their patients’ eligibility for CT evaluated based on functional status, comorbidities, age, advanced cancer stage, progression of disease, change in therapy, and drug targets. Conclusions: We identified actionable enabling, predisposing, and need factors that serve as barriers to CT accrual and to successful implementation of our intervention. Major findings were structural and attitudinal, including lack of staffing resources for clinicians, and financial assistance and access for patients. Updated information about open CTs, implementation of e-screening tools for patient enrollment, addressing clinician skepticism for enrollment by increased recognition for their research efforts, as well as delivery of culturally sensitive patient education around CTs may improve CT enrollment.
Endostatin in combination with PD-1 antibody plus chemotherapy as first-line regimen for EGFR/ALK-negative, advanced or metastatic non-small cell lung cancer: A real-world study.
Authors: Jing Zhang, Shengjie Sun, Xiao Zhao, Minglu Liu, Lupeng Qiu, Zizhong Yang, Guoqing Zhang
Journal: Journal of Clinical Oncology (2023)

e20564 Background: In recent years, treatment for advanced or metastatic NSCLC has been significantly improved with the emergence of a combination strategy of immunotherapy with antiangiogenic drugs plus chemotherapy. Although endostatin (an antiangiogenic agent) combined with chemotherapy has been approved by the China Food and Drug Administration in treatment-naïve and re-treatment NSCLC patients, the clinical evidence supporting its combination with programmed cell death-1 (PD-1) antibody for advanced or metastatic NSCLC is still insufficient. Therefore, we aimed to evaluate the effectiveness and safety of endostatin combined with PD-1 antibody plus chemotherapy as the first-line treatment for locally advanced or distant metastatic NSCLC with EGFR/ALK-negative. Methods: This was a retrospective, singer-center, real-world study conducted between June 2018 and December 2021. The primary endpoint was progression-free survival (PFS); the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: Overall, 68 patients were included. The median PFS and OS were 22.0 months (95% confidence interval [CI]: 16.6-27.4 months) and 31.0 months (95% CI: 23.4 months-not reached [NR]), respectively, with a median follow-up of 21.4 months (range, 8.3-44.4 months). At the data cutoff, 33 patients (48.5%) remained progression-free and 24 patients (35.3%) had died. Short-term clinical efficacy was assessed after 2 consecutive treatment cycles, with an ORR of 72.06% (complete response [CR], n = 3; partial response [PR], n = 46) and a DCR of 95.59% (CR, n = 3; PR, n = 46; stable disease, n = 16). Further subgroup analysis determined that a significantly better ORR (89.2% vs. 51.6%), median PFS (23.4 vs. 13.2 months), and median OS (NR vs. 18.0 months) for patients with stage Ⅲ B/Ⅲ C vs. stage Ⅳ NSCLC (all p ≤ 0.001). Besides, the median PFS (8.0 months vs. 22.5 months, p = 0.004) and OS (13.0 vs. 31.0 months, p = 0.027) of patients with brain metastasis were significantly shorter than those without brain metastasis. The ORR in patients who had a PD-L1 tumor proportion score (TPS) of &lt; 1%, 1%-49%, ≥ 50%, and unknown were 50%, 50%, 75.0%, and 86.1%, respectively ( p = 0.025). All patients (100%) experienced treatment-related adverse events (AEs). The majority of AEs were grade 1 or 2 (57/68, 83.82%). Conclusions: In the real-world scenario, endostatin combination with PD-1 antibody plus chemotherapy obtained encouraging efficacy and favorable safety in advanced or metastatic NSCLC. The combination strategy in this study furnished beneficial evidence for the treatment of advanced or metastatic NSCLC and is essential for determining the best treatment option.
Feasibility of integrating geriatric oncology and palliative care assessment into the routine care of older adults in a community setting.
Authors: Ramy Sedhom, Noah A. Goldman, Kerri Celaya, Kari A Mastro, Paul Ortiz, David W. Dougherty
Journal: Journal of Clinical Oncology (2023)

e24024 Background: Emerging data support the value of geriatric assessment (GA) and palliative care (PC) domains in determining treatment for older adults with cancer. Limited data exist on the ability to integrate GA and PC in a community oncology clinic. The objective of this study was to determine the feasibility of integrating GA and PC screening in the community. Methods: Patients ≥ 75 were eligible. The GA included a health care provider assessment of performance status, cognitive function, functional status, psychological state, social support, and nutritional status. PC assessment included ESAS questionnaire, patient goals and values, advance care plans, and caregiver distress. Results: From September 2021 to Jan 2023, 131 consecutive older adults were assessed in one community clinic in the State of New Jersey, a satellite of the University of Pennsylvania. The median age was 82 (range 75-97). Using the VES-13 survey, 11% of patients were fit, 60% vulnerable and 29% frail. Issues were noted in cognition (11%), psychological state (27%), social support (38%), and nutrition (26%). The majority of patients prioritized quality of life over time (73%) and maintenance of independence was often cited as the most important goal (62%). Fewer than half of patients had formal advance directives (42%). 32% of the time, the final plan deviated from standard of care to align with patient/caregiver values. Conclusions: Integration of GA and PC is feasible in the community oncology setting. Further study is planned to evaluate the impact on patient and caregiver outcomes, and to standardize assessment for routine care across all Penn Medicine clinics.